Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
JAMA Psychiatry. 2021 Jul 1;78(7):753-766. doi: 10.1001/jamapsychiatry.2021.0638.
The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.
To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).
DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.
Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).
Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001).
This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
ENIGMA 临床高风险（CHR）精神分裂症倡议是迄今为止最大的 CHR 神经影像学样本库，旨在发现精神分裂症风险的稳健神经生物学标志物。
研究 CHR 个体与健康对照组之间以及后来发展为精神病障碍（CHR-PS+）和未发展为精神病障碍（CHR-PS-）的 CHR 参与者之间的基线结构神经影像学差异。
设计、地点和参与者：在这项病例对照研究中，从参与 ENIGMA 临床高风险精神分裂症工作组的 31 个国际站点汇总了基线 T1 加权磁共振成像（MRI）数据。使用全面评估风险精神状态或结构化前驱综合征访谈来评估 CHR 状态。使用协调的协议处理 MRI 扫描，并在 2020 年 1 月至 10 月期间在 mega 分析和荟萃分析框架内进行分析。
从 T1 加权 MRI 扫描中提取了区域皮质厚度（CT）、表面积和皮质下体积的测量值。自变量为组（CHR 组与对照组）和转换状态（CHR-PS+组与 CHR-PS-组与对照组）。
在纳入的 3169 名参与者中，1428 名（45.1%）为女性，平均（SD；范围）年龄为 21.1（4.9；9.5-39.9）岁。本研究包括 1792 名 CHR 患者和 1377 名健康对照者。使用纵向临床信息，确定了 253 名 CHR-PS+组、1234 名 CHR-PS-组和 305 名 CHR 无随访数据的患者。与健康对照组相比，CHR 患者表现出广泛的 CT 测量值降低（平均[范围]Cohen d = -0.13[-0.17 至-0.09]），但表面积或皮质下体积没有降低。梭状回、上颞叶和旁中央区域的 CT 测量值降低与精神病转化相关（平均 Cohen d = -0.22；95%CI，-0.35 至 0.10）。在健康对照组中，与 CHR-PS+组相比，年龄与左侧梭状回 CT 测量值（F = 9.8；P <.001；q <.001）和左侧旁中央 CT 测量值（F = 5.9；P =.005；q =.02）呈更强的负相关。与精神病转化相关的 CT 较低的效应大小与 ENIGMA 精神分裂症研究中观察到的 CT 差异模式相似（ρ=0.35；95%CI，0.12 至 0.55；P =.004）和 22q11.2 微缺失综合征伴精神病诊断的个体（ρ=0.43；95%CI，0.20 至 0.61；P =.001）。
本研究为 CHR 患者广泛存在轻微、较低的 CT 测量值提供了证据。CHR-PS+组的 CT 测量值差异模式与其他大型精神病研究报告的模式相似。此外，这些区域中的一部分显示出异常的年龄相关性。CHR 患者的 CT 广泛破坏以及与年龄的异常相关性可能表明出生后大脑发育过程的破坏。
